The accurate measurement of the concentration of chiral molecules in a solution by a polarimeter is required in applications such as the synthesis of organic molecules, where the outcome of a reaction is a racemic mixture of both enantiomers, which have identical physicochemical characteristics except for the rotation of linearly polarized light. Enantiomers also interact differently with biological enzymes. Therefore, the ability to distinguish between the two enantiomers is especially crucial in the pharmaceutical industry, where in many cases only one enantiomer has the desired activity while the other can be highly toxic, although both are physically identical.
A more sensitive and accurate polarimeter may mean lower concentrations of precious reagents, faster development processes, and purer, safer products.
Polarimeters based on coherent detection (Jacobs, S. F., (1988), Optical heterodyne (coherent) detection, Am. J. Phys., 56 (3): 235-245, and King, H. J., Chou, C., and Lu, S. T., Optical heterodyne polarimeter for measuring the chiral parameter and the circular refraction indices of optical activity, Opt. Lett., 1993, 18: 1970-1972), have the advantage of being sensitive and accurate without any moving mechanical parts, which are required by ordinary polarimeters in order to rotate polarizers or move quartz plates. They also do not rely on bulky optical components, like Faraday rotators, which can be found in modern advanced polarimeters.
U.S. Pat. Nos. 5,896,198 and 6,327,037 disclose a heterodyne polarimeter employing a two-frequency laser source and a common path interferometer. However, this polarimeter cannot distinguish between a heterodyne signal resulting from increased optical activity in the solution or one resulting from increased polarization noise (i.e. anything other than optical activity allowing more light to reach the detector through the analyzer), which adds to the detected coherent signal. Such sources can be, for example, the finite extinction ratio of the polarizers, depolarization of the linearly polarized laser beam by scattering, temperature-dependent birefringence in optical elements and the practical imperfection of Zeeman lasers. These limitations can become important especially when reference (blank) samples cannot be measured. U.S. Pat. No. 6,188,477 discloses a polarimeter based on a self-homodyne scheme. Here too no distinction can be made between the optical activity dependent signal and signals generated by increased depolarization or phase noise in the optical system. This polarimeter also is likely to be sensitive to mechanical phase noise in the optical setup responsible for the phase modulation.
Recently, the inventors disclosed a polarimeter for quantitative measurement of the concentration of optically active substances in a solution by incorporating a Mach-Zehnder interferometer into a polarimeter (WO 2008/018079).